Project Summary The long term objective of the proposed research is to develop a new means for diabetic patients to painlessly and non-invasively monitor their blood glucose levels. There is convincing evidence that when diabetes patients actively monitor and control their blood glucose levels, long term complications including retinopathy and neuropathy can be avoided. Current monitoring technologies require the patient to prick their finger to extract blood, which can discourage a patient from actively monitoring their glucose levels. In this exploratory project, a novel method is proposed for noninvasive glucose monitoring. The method is based on the measurement and analysis of otoacoustic emissions (OAE). The OAE is a low-intensity sound generated by the cochlea in response to acoustic stimuli. Evoking and measuring an OAE is done using a tiny speaker and microphone that fits snugly inside of the ear. There is evidence from the literature that the temporal and spectral components of an OAE correlate with vascular glucose levels. This was confirmed in an animal study using rabbits. A single study investigating the link between OAEs and glucose in human diabetic subjects, however, did not show significant correlation. However, no studies have been performed which considered suppressed OAEs. The OAE response can be partially suppressed or masked by presenting a competing acoustic stimulus either contralaterally (opposite ear), ipsilaterally (same ear), or both. This suppression effect has been shown to be a result of neural efferent feedback from the brain. Neural effects including evoked responses and axonal transmission latencies are known to correlate with glucose. This suggests that suppressed OAEs may provide a robust correlation with glucose since the suppression is a result of peripheral neural feedback, and neural activity is affected by glucose levels. Preliminary experiments presented here provide strong evidence to support this hypothesis. This grant proposes additional more detailed experiments and evaluations. Specific aims include (1) determining optimal procedures for evoking and measuring suppressed OAEs that best correlate with blood glucose in diabetic and nondiabetic subjects, (2) developing parametric and non-parametric models to predict blood glucose levels, and (3) evaluating the prediction models based on clinical accuracy measures. Research methods include a number of experiments in which diabetic and non-diabetic subjects will be given a glucose tolerance test while suppressed and unsuppressed OAEs are measured. Signal processing algorithms will be applied to the OAE waveforms to evaluate how well temporal and spectral patterns correlate with blood glucose during the test. Control experiments will be done and potential interfering compounds will be independently assessed. The outcome from this research could ultimately lead to the future development of a low-cost, hand-held device that would be used by diabetic patients to painlessly and noninvasively monitor their glucose levels. Project Narrative/Relevance:Studies have shown that persons with diabetes can reduce the risk of complications associated with the disease significantly by actively monitoring their blood sugar levels. However, many diabetic patients fail to monitor their blood sugar for the primary reasons of finger soreness, pain, inconvenience, or fear of needles. In this project, a new method for enabling diabetic patients to painlessly and non-invasively monitor their glucose levels is proposed which uses low intensity sounds emitted from the ears. [unreadable] [unreadable] [unreadable] [unreadable]